scholarly journals Malaria is associated with Kaposi sarcoma-associated herpesvirus (KSHV) seroconversion in a cohort of western Kenyan children

Author(s):  
Katherine R Sabourin ◽  
Ibrahim Daud ◽  
Sidney Ogolla ◽  
Nazzarena Labo ◽  
Wendell Miley ◽  
...  

Abstract Background We aimed to determine whether Plasmodium falciparum (Pf) infection affects age of Kaposi sarcoma-associated herpesvirus (KSHV) seroconversion in Kenyan children. Methods Kenyan children (n=144) enrolled at age one month, from two sites with different levels of malaria transmission (stable/high malaria vs. unstable/low malaria transmission) were followed through 24 months. Plasma was tested for KSHV antibodies using enzyme-linked immunosorbent assay (ELISA) (K8.1 and LANA) and a multiplex bead-based assay (K8.1, K10.5, ORF38, ORF50, and LANA) and whole blood tested for Pf DNA using quantitative-PCR. Cox proportional hazards models were used to assess associations between Pf DNA detection, malaria annualized rate (Pf detections/person-years), and enrollment site (malaria-high vs malaria-low) with time to KSHV seroconversion. Results KSHV seroprevalence was 63% by 2 years of age when assessed by multiplex assay. Children with Pf were at increased hazards of earlier KSHV seroconversion and among children with malaria, the hazard of becoming KSHV seropositive increased significantly with increasing malaria annualized rate. Children from the malaria-high transmission region had no significant difference in hazards of KSHV seroconversion at 12 months but were more likely to become KSHV seropositive by 24 months of age. Discussion Malaria exposure increases the risk for KSHV seroconversion early in life.

BMJ Open ◽  
2019 ◽  
Vol 9 (3) ◽  
pp. e025124 ◽  
Author(s):  
Takako Fujita ◽  
Akira Babazono ◽  
Yumi Harano ◽  
Peng Jiang

ObjectiveWe sought to examine the effect of smoking cessation on subsequent development of depressive disorders.DesignThis was a retrospective cohort study.MethodsWe used administrative claim and health check data from fiscal years 2010 to 2014, obtained from the largest health insurance association in Fukuoka, Japan. Study participants were between 30 and 69 years old. The end-point outcome was incidence of depressive disorders. Survival analysis and Cox proportional hazards models were conducted. The evaluated potential confounders were sex, age, standard monthly income and psychiatric medical history.ResultsThe final number of participants was 87 255, with 7841 in the smoking cessation group and 79 414 in the smoking group. The result of survival analysis showed no significant difference in depressive disorders between the two groups. The results of Cox proportional hazards models showed no significant difference by multivariate analysis between participants, including users of smoking cessation medication (HR 1.04, 95% Cl 0.89 to 1.22) and excluding medication use (HR 0.97, 95% Cl 0.82 to 1.15).ConclusionsThe present study showed that there were no significant differences with respect to having depressive disorders between smoking cessation and smoking groups. We also showed that smoking cessation was not related to incidence of depressive disorders among participants, including and excluding users of smoking cessation medication, after adjusting for potential confounders. Although the results have some limitations because of the nature of the study design, our findings will provide helpful information to smokers, health professionals and policy makers for improving smoking cessation.


2021 ◽  
Vol 8 ◽  
Author(s):  
Menghui Liu ◽  
Shaozhao Zhang ◽  
Xiaohong Chen ◽  
Xiangbin Zhong ◽  
Zhenyu Xiong ◽  
...  

Background: The elevated blood pressure (BP) at midlife or late-life is associated with cardiovascular disease and death. However, there is limited research on the association between the BP patterns from middle to old age and incident coronary heart disease (CHD) and death.Methods: A cohort of the Atherosclerosis Risk in Communities (ARIC) Study enrolled 9,829 participants who attended five in-person visits from 1987 to 2013. We determined the association of mid- to late-life BP patterns with incident CHD and all-cause mortality using multivariable-adjusted Cox proportional hazards models.Results: During a median of 16.7 years of follow-up, 3,134 deaths and 1,060 CHD events occurred. Compared with participants with midlife normotension, the adjusted hazard ratio for all-cause mortality and CHD was 1.14 (95% CI, 1.04–1.25) and 1.28 (95% CI, 1.10–1.50) in those with midlife hypertension, respectively. In further analyses, compared with a pattern of sustained normotension from mid- to late-life, there was no significant difference for the risk of incident death (HR, 1.15; 95% CI, 0.96–1.37) and CHD (HR, 1.33; 95% CI, 0.99–1.80) in participants with a pattern of midlife normotension and late-life hypertension with effective BP control. A higher risks of death and CHD were found in those with pattern of mid- to late-life hypertension with effective BP control (all-cause mortality: HR, 1.24; 95% CI, 1.08–1.43; CHD: HR, 1.65; 95% CI 1.30–2.09), pattern of midlife normotension and late-life hypertension with poor BP control (all-cause mortality: HR, 1.27; 95% CI, 1.12–1.44; CHD: HR, 1.53; 95% CI, 1.23–1.92), and pattern of mid- to late-life hypertension with poor BP control (all-cause mortality: HR, 1.49; 95% CI, 1.30–1.71; CHD: HR, 1.87; 95% CI, 1.48–2.37).Conclusions: The current findings underscore that the management of elderly hypertensive patients should not merely focus on the current BP status, but the middle-aged BP status. To achieve optimal reductions in the risk of CHD and death, it may be necessary to prevent, diagnose, and manage of hypertension throughout middle age.


2017 ◽  
Vol 35 (6_suppl) ◽  
pp. 14-14 ◽  
Author(s):  
Cameron Ghaffary ◽  
Tamer Dafashy ◽  
Christopher David Kosarek ◽  
Zhigang Duan ◽  
Brian F. Chapin ◽  
...  

14 Background: National Cancer Institute (NCI) and National Comprehensive Cancer Network (NCCN)-designated cancer centers (CCs) offer patients state-of-the-art treatment. We sought to identify whether proximity to NCI/NCCN CCs was associated with survival outcomes for prostate cancer patients who undergo radical prostatectomy (RP). Methods: A total of 12,478 total patients diagnosed with clinical stage T1 or T2 prostate cancer between 2004–2011 using linked Surveillance, Epidemiology, and End Results (SEER)-Medicare data were included. Multivariable regression analyses were used to quantify overall survival and use of secondary therapies for RP patients according to proximity to NCI/NCCN CCs. Cox proportional hazards models were used to quantify the association between survival outcomes and access to NCI/NCCN CCs. Results: Patients with proximity to ≥ 2 NCI centers and those diagnosed in 2011 enjoyed a statistically significant overall survival advantage when compared to no access to an NCI center (Hazard Ratio (HR) 0.72; 95% confidence interval (CI) 0.57–0.92, p < 0.01). Proximity to an NCCN CC, when compared with men who did not have access, was associated with improved overall survival (HR 0.76; 95% CI 0.61–0.95, p = 0.015). There was no significant difference in use of secondary therapies according to NCI or NCCN access. Conclusions: Patients who undergo RP with access to an NCI/NCCN CCs experienced improved overall survival with no significant difference in utilization of secondary therapies. Given the need for improved health quality measures in cancer care, these findings may support health policy implementation and regionalization of care to these centers.


2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 5527-5527 ◽  
Author(s):  
Emmanuel S. Antonarakis ◽  
Russell Madison ◽  
Jeremy Snider ◽  
Tamara Snow ◽  
Ethan Sokol ◽  
...  

5527 Background: Inactivating alts in BRCA1/2 result in homologous recombination deficiency and are predictive of PARPi response in mCRPC. BRCA reversion mutations, which restore the protein function, are frequently observed in acquired resistance to PARPi. In tumors harboring homozygous gene deletions ( BRCAdel) reversions cannot develop; thus, we hypothesize that BRCAdel pts may have prolonged benefit from PARPi compared to pts harboring other BRCA alterations. Methods: Pts were included from the Flatiron Health (FH)-Foundation Medicine (FMI) de-identified clinico-genomic database (CGDB). Inclusion criteria were diagnosis of mCRPC, treatment in the FH network and an FMI comprehensive genomic profiling result between 1/1/2011 - 9/30/2019. Time to therapy discontinuation (TTD) and overall survival (OS) from start of PARPi were estimated with Kaplan-Meier analysis and unadjusted/adjusted (age at PARPi initiation, line number, practice type) hazard ratios (HR/aHR) from Cox proportional hazards models adjusted for survival bias. Results: Out of 829 mCRPC cases, BRCA1/2 alts were detected in 15 (1.8%) and 71 (8.6%) respectively, with 2 cases included in both groups. 26% of BRCAalts were BRCAdel, 67% were coding mutations, and 7% were genomic rearrangements. 25 (28%) BRCAalt pts were treated with PARPi, 11/25 in the 1st or 2nd line setting including 43% of BRCAdel and 44% of other BRCAalt cohorts. Median age at PARPi initiation was 70 yrs and 88% were treated in community practices. TTD was significantly longer in the BRCAdel (n = 7) cohort vs. other BRCAalt cohort (n = 18) (22.7 vs. 9.2 months; HR: 0.16 [0.03-0.74]; aHR: 0.13 [0.02 – 0.92]) while a statistically nonsignificant difference in median OS was observed (31.5 vs. 11.9 months; HR: 0.20 [0.02-1.58]; aHR: 0.24 [0.02-3.15]). In comparison, no statistically significant difference in TTD was observed for BRCAdel (n= 7) vs. other BRCAalts (n=19) pts treated with 1st line hormonal therapies (abiraterone or enzalutamide) (3.4 vs. 5.7 months; HR: 1.16 [0.45-2.98]; aHR: 0.72 [0.25-2.10]). Follow up analysis with more pts and somatic/germline status and zygosity of BRCAalts will be presented. Conclusions: These data suggest a differential benefit from PARPi therapy across BRCAalt subgroups. This observation may in part be explained by the inability to develop reversion mutations to restore BRCA function in tumors with BRCAdel. Further studies are warranted to fully assess the association of BRCAalt type with outcomes to PARPi-based treatments.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Jing Gong ◽  
Ding-kun Wang ◽  
Hui Dong ◽  
Qing-song Xia ◽  
Zhao-yi Huang ◽  
...  

Abstract Background Low free triiodothyronine (FT3) levels are related to a poor prognosis deterioration in patients with COVID-19 presenting with non-thyroidal illness syndrome (NTI). This study was designed to explore whether free thyroxin (FT4) or thyroid stimulating hormone (TSH) levels affected the mortality of patients with COVID-19 presenting with NTI. Methods Patients with COVID-19 complicated with NTI who were treated at our hospital were included in this retrospective study. Patients were divided into low TSH and normal TSH groups, as well as low and normal-high FT4 group, according to the reference range of TSH or FT4 levels. The 90-day mortality and critical illness rates were compared among patients with low and normal TSH levels, as well as among patients with low FT4 levels and normal-high FT4 levels; in addition, differences in demographic and laboratory data were compared. A Kaplan-Meier analysis and Cox proportional hazards models were used to assess the associations of TSH and FT4 levels with mortality. Results One hundred fifty patients with low FT3 levels and without a history of thyroid disease were included, 68% of whom had normal FT4 and TSH levels. Critical illness rates (74.07% VS 37.40%, P = 0.001) and mortality rates (51.85% VS 22.76%, P = 0.002) were significantly higher in the low TSH group than in the normal TSH group. Although no significant difference in the critical illness rate was found (P = 0.296), the mortality rate was significantly higher in the low FT4 group (P = 0.038). Low TSH levels were independently related to 90-day mortality (hazard ratio = 2.78, 95% CI:1.42–5.552, P = 0.003). Conclusions Low FT4 and TSH concentrations were associated with mortality in patients with COVID-19 presenting with NTI; moreover, low TSH levels were an independent risk factor for mortality in these patients.


2001 ◽  
Vol 19 (4) ◽  
pp. 931-942 ◽  
Author(s):  
Bernard Fisher ◽  
Stewart Anderson ◽  
Elizabeth Tan-Chiu ◽  
Norman Wolmark ◽  
D. Lawrence Wickerham ◽  
...  

PURPOSE: Uncertainty about the relative worth of doxorubicin/cyclophosphamide (AC) and cyclophosphamide/methotrexate/fluorouracil (CMF), as well as doubt about the propriety of giving tamoxifen (TAM) with chemotherapy to patients with estrogen receptor–negative tumors and negative axillary nodes, prompted the National Surgical Adjuvant Breast and Bowel Project to initiate the B-23 study. PATIENTS AND METHODS: Patients (n = 2,008) were randomly assigned to CMF plus placebo, CMF plus TAM, AC plus placebo, or AC plus TAM. Six cycles of CMF were given for 6 months; four cycles of AC were administered for 63 days. TAM was given daily for 5 years. Relapse-free survival (RFS), event-free survival (EFS), and survival (S) were determined by using life-table estimates. Tests for heterogeneity of outcome used log-rank statistics and Cox proportional hazards models to detect differences across all groups and according to chemotherapy and hormonal therapy status. RESULTS: No significant difference in RFS, EFS, or S was observed among the four groups through 5 years (P = .96, .8, and .8, respectively), for those aged ≤ 49 years (P = .97, .5, and .9, respectively), or for those aged ≥ 50 years (P = .7, .6, and .6, respectively). A comparison between all CMF- and all AC-treated patients demonstrated no significant differences in RFS (87% at 5 years in both groups, P = .9), EFS (83% and 82%, P = .6), or S (89% and 90%, P = .4). There were no significant differences in RFS, EFS, or S between CMF and AC in patients aged ≤ 49 or ≥ 50 years. No significant difference in any outcome was observed when chemotherapy-treated patients who received placebo were compared with those given TAM. RFS in both groups was 87% (P = .6), 87% in patients aged ≤ 49 (P = .9), and 88% and 87%, respectively (P = .4), in those aged ≥ 50 years. CONCLUSION: There was no significant difference in the outcome of patients who received AC or CMF. TAM with either regimen resulted in no significant advantage over that achieved from chemotherapy alone.


2020 ◽  
Vol 2020 ◽  
pp. 1-7
Author(s):  
Yanhua Yang ◽  
Suxia Guo ◽  
Ziyao Huang ◽  
Chunhua Deng ◽  
Lihua Chen ◽  
...  

Background. There are no proven effective treatments that can reduce the mortality in heart failure with preserved ejection fraction (HFpEF), probably due to its heterogeneous nature which will weaken the effect of therapy in clinical studies. We evaluated the effect of beta-blocker treatment in HFpEF patients associated with atrial fibrillation (AF), which is a homogeneous syndrome and has seldom been discussed. Methods. This retrospective cohort study screened 955 patients diagnosed with AF and HFpEF. Patients with a range of underlying heart diseases or severe comorbidities were excluded; 191 patients were included and classified as with or without beta-blocker treatment at baseline. The primary outcome was all-cause mortality and rehospitalization due to heart failure. Kaplan-Meier curves and multivariable Cox proportional-hazards models were used to evaluate the differences in outcomes. Results. The mean follow-up was 49 months. After adjustment for multiple clinical risk factors and biomarkers for prognosis in heart failure, patients with beta-blocker treatment were associated with significantly lower all-cause mortality (hazard ratio (HR) = 0.405, 95% confidence interval (CI) = 0.233–0.701, p=0.001) compared with those without beta-blocker treatment. However, the risk of rehospitalization due to heart failure was increased in the beta-blocker treatment group (HR = 1.740, 95% CI = 1.085–2.789, p=0.022). There was no significant difference in all-cause rehospitalization between the two groups (HR = 1.137, 95% CI = 0.803–1.610, p=0.470). Conclusions. In HFpEF patients associated with AF, beta-blocker treatment is associated with significantly lower all-cause mortality, but it increased the risk of rehospitalization due to heart failure.


Sexual Health ◽  
2011 ◽  
Vol 8 (3) ◽  
pp. 295 ◽  
Author(s):  
Sadaf Marashi Pour ◽  
Ian Woolley ◽  
Peter Canavan ◽  
John Chuah ◽  
Darren B. Russell ◽  
...  

Background Patients who have become triple class experienced (TCE) are at a high risk of exhausting available treatment options. This study aims to investigate factors associated with becoming TCE and to explore the effect of becoming TCE on survival. We also project the prevalence of TCE in Australia to 2012. Methods: Patients were defined as TCE when they stopped a combination antiretroviral treatment (cART) that introduced the third of the three major antiretroviral classes. Cox proportional hazards models were used to investigate factors associated with TCE and the effect of TCE on survival. To project TCE prevalence, we used predicted rates of TCE by fitting a Poisson regression model, together with the estimated number of patients who started cART in each year in Australia, assuming a mortality rate of 1.5 per 100 person-years. Results: Of the 1498 eligible patients, 526 became TCE. Independent predictors of a higher risk of TCE included current CD4 counts below 200 cells μL–1 and earlier calendar periods. No significant difference in survival was observed between those who were TCE and those who were not yet TCE. An increasing number of patients are using cART in Australia and if current trends continue, the number of patients who are TCE is estimated to increase from 2800 in 2003 to 5000 in 2012. Conclusion: Our results suggest that the prevalence of TCE in Australia is estimated to plateau after 2003. However, as an increasing number of patients are becoming TCE, it is necessary to develop new drugs that come from new classes or do not have overlapping resistance.


JAMIA Open ◽  
2020 ◽  
Author(s):  
Spiros Denaxas ◽  
Anoop D Shah ◽  
Bilal A Mateen ◽  
Valerie Kuan ◽  
Jennifer K Quint ◽  
...  

Abstract Objectives The UK Biobank (UKB) is making primary care electronic health records (EHRs) for 500 000 participants available for COVID-19-related research. Data are extracted from four sources, recorded using five clinical terminologies and stored in different schemas. The aims of our research were to: (a) develop a semi-supervised approach for bootstrapping EHR phenotyping algorithms in UKB EHR, and (b) to evaluate our approach by implementing and evaluating phenotypes for 31 common biomarkers. Materials and Methods We describe an algorithmic approach to phenotyping biomarkers in primary care EHR involving (a) bootstrapping definitions using existing phenotypes, (b) excluding generic, rare, or semantically distant terms, (c) forward-mapping terminology terms, (d) expert review, and (e) data extraction. We evaluated the phenotypes by assessing the ability to reproduce known epidemiological associations with all-cause mortality using Cox proportional hazards models. Results We created and evaluated phenotyping algorithms for 31 biomarkers many of which are directly related to COVID-19 complications, for example diabetes, cardiovascular disease, respiratory disease. Our algorithm identified 1651 Read v2 and Clinical Terms Version 3 terms and automatically excluded 1228 terms. Clinical review excluded 103 terms and included 44 terms, resulting in 364 terms for data extraction (sensitivity 0.89, specificity 0.92). We extracted 38 190 682 events and identified 220 978 participants with at least one biomarker measured. Discussion and conclusion Bootstrapping phenotyping algorithms from similar EHR can potentially address pre-existing methodological concerns that undermine the outputs of biomarker discovery pipelines and provide research-quality phenotyping algorithms.


Cancers ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 1177
Author(s):  
In Young Choi ◽  
Sohyun Chun ◽  
Dong Wook Shin ◽  
Kyungdo Han ◽  
Keun Hye Jeon ◽  
...  

Objective: To our knowledge, no studies have yet looked at how the risk of developing breast cancer (BC) varies with changes in metabolic syndrome (MetS) status. This study aimed to investigate the association between changes in MetS and subsequent BC occurrence. Research Design and Methods: We enrolled 930,055 postmenopausal women aged 40–74 years who participated in a biennial National Health Screening Program in 2009–2010 and 2011–2012. Participants were categorized into four groups according to change in MetS status during the two-year interval screening: sustained non-MetS, transition to MetS, transition to non-MetS, and sustained MetS. We calculated multivariable-adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for BC incidence using the Cox proportional hazards models. Results: At baseline, MetS was associated with a significantly increased risk of BC (aHR 1.11, 95% CI 1.06–1.17) and so were all of its components. The risk of BC increased as the number of the components increased (aHR 1.46, 95% CI 1.26–1.61 for women with all five components). Compared to the sustained non-MetS group, the aHR (95% CI) for BC was 1.11 (1.04–1.19) in the transition to MetS group, 1.05 (0.96–1.14) in the transition to non-MetS group, and 1.18 (1.12–1.25) in the sustained MetS group. Conclusions: Significantly increased BC risk was observed in the sustained MetS and transition to MetS groups. These findings are clinically meaningful in that efforts to recover from MetS may lead to reduced risk of BC.


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